Autologous Stem Cell Transplantation (AuSCT) for Multiple Myeloma (MM)

To the Centers for Medicare & Medicaid Services:

I am a physician specializing in multiple myeloma and hematopoietic cell transplantation at the Fred Hutchinson Cancer Center. I strongly support CMS’s reconsideration of National Coverage Determination (NCD) 110.23. However, the proposed revision—adding the International Staging System (ISS) alongside Durie-Salmon stage II/III—preserves the central flaw in the current policy: prognostic stage should not determine Medicare coverage for autologous stem cell transplantation (ASCT).

The historical reason for the Durie-Salmon restriction is important. When Durie-Salmon staging was introduced in 1975, smoldering multiple myeloma had not yet been defined. Durie-Salmon stage I therefore included a heterogeneous mixture of patients with active myeloma and patients who today would be classified as having smoldering myeloma. Excluding stage I patients from the early pivotal ASCT trials was reasonable because investigators appropriately sought to avoid exposing patients with asymptomatic disease to high-dose chemotherapy. Those trial eligibility criteria ultimately became embedded in the NCD.

That problem has since been solved—not by a newer prognostic staging system, but by modern diagnostic criteria. The International Myeloma Working Group now clearly distinguishes smoldering from active multiple myeloma using SLiM/CRAB criteria. ISS and its revisions serve a different purpose: they estimate prognosis after active myeloma has been diagnosed. An ISS stage I patient with SLiM/CRAB-defined active myeloma is therefore fundamentally different from the heterogeneous Durie-Salmon stage I population that motivated the original restriction. Treating the two staging systems as interchangeable is an apples-to-oranges comparison.

Contemporary randomized evidence also demonstrates that ASCT benefit is not confined to higher ISS stages. IFM 2009 showed improved progression-free survival (PFS) with upfront ASCT, including in the prespecified ISS stage I subgroup (Attal et al., N Engl J Med. 2017). DETERMINATION confirmed a substantial PFS benefit with upfront ASCT, again including ISS stage I disease (Richardson et al., N Engl J Med. 2022). EMN02/HO95 demonstrated improved PFS with ASCT versus non-transplant intensification across ISS stages I–III (Cavo et al., Lancet Haematol. 2020), and FORTE likewise supported upfront ASCT across ISS subgroups, including stage I (Gay et al., Lancet Oncol. 2021). These trials provide no evidence basis for denying ASCT coverage solely because a patient with active myeloma has favorable prognostic stage.

The proposed policy would therefore create a new and clinically unjustified exclusion: Medicare beneficiaries with unequivocally active, treatment-requiring myeloma could be denied ASCT simply because they have ISS stage I disease. Favorable prognosis is not evidence that transplantation is unnecessary.

I urge CMS to eliminate stage-based eligibility requirements rather than substitute ISS for Durie-Salmon. Coverage should be based on (1) active multiple myeloma requiring therapy by contemporary diagnostic criteria, including SLiM/CRAB; and (2) clinical appropriateness for high-dose therapy and ASCT as determined by a transplant physician, considering disease status, performance status, comorbidities, organ function, and overall fitness.

At minimum, CMS should explicitly cover ASCT for patients with active multiple myeloma across ISS stages I, II, and III. The more durable solution is to remove prognostic stage from the coverage determination entirely. This would preserve the original policy’s appropriate intent—avoiding high-dose therapy for patients without treatment-requiring disease—while aligning Medicare coverage with modern myeloma diagnosis, randomized evidence, and clinical practice.

Thank you for your consideration.

Sincerely,

Andrew Portuguese, MD
Assistant Professor
Fred Hutchinson Cancer Center

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I am a physician specialized in multiple myeloma with ample explerience in all aspects of care including autologous stem cell transplantation. The role of transplant in general is being questioned in a series of ongoing, well designed clinical trials. At present time autologous transplantation is an evidence-based, safe and, when compared to newer therapies, affordable treatment that extends PFS . There is no evidence limiting the benefit of transplantation to patients with Durie-Salmon stages 2 and 3. In fact, this very staging system is outdated, has little prognostic value and was never predictive of benefit of stem cell transplantation. Coverage for transplantation should apply to patients with symptomatic myeloma, irrespective of staging.

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August 11, 2026
Centers for Medicare & Medicaid Services
Coverage and Analysis Group
7500 Security Boulevard
Baltimore, MD 21244

Re: Proposed Decision Memorandum CAG-00444R2, Autologous Stem Cell Transplantation (AuSCT) for Multiple Myeloma
To the Coverage and Analysis Group:

I am a Professor of Medicine and staff physician in Hematology/Oncology and Stem Cell Transplantation at the Cleveland Clinic Taussig Cancer Center, where I direct the inpatient lymphoma and myeloma service. I have cared for Medicare beneficiaries undergoing autologous transplantation for myeloma throughout my career, and I write to comment on the proposed revision to NCD 110.23, section B.II.b.

I support CMS's decision to move beyond the Durie-Salmon staging system, which has been abandoned in clinical practice for the reasons the memorandum lays out. However, the proposed manual language, which covers single AuSCT only for “Stage II or III patients using Durie Salmon or International Staging System and its revisions,” would create a serious new problem while fixing an old one. It would, for the first time, remove guaranteed coverage from ISS stage I beneficiaries. I urge CMS to remove staging as a coverage criterion entirely, or, at minimum, to state explicitly that ISS stages I, II, and III are all covered.

First, staging in myeloma is prognostic, not predictive of transplant benefit. The ISS and its revisions were built to estimate survival, not to select transplant candidates, and the memorandum's own evidence review evaluates them as prognostic tools. None of the randomized trials that established autologous transplantation as standard of care restricted enrollment by stage, and the progression-free survival benefit of transplant was observed across risk groups. In the DETERMINATION trial (Richardson et al., N Engl J Med 2022;387:132-147), patients across all ISS stages, including stage I, derived benefit from transplantation. A stage I patient is not a patient who needs transplant less. She / he is often the patient who gains the longest remission from it.

Second, the proposed change is a contraction disguised as an expansion. Durie-Salmon stage I describes low-burden disease that today rarely meets IMWG criteria for treatment at all, so under the current NCD nearly every symptomatic patient fell into DS stage II or III and the restriction excluded almost no one. ISS stage I is different: it is defined only by a beta-2 microglobulin below 3.5 mg/L and albumin of 3.5 g/dL or higher, and it accounts for roughly one third of newly diagnosed patients. Carrying the words “stage II or III” from one system to the other transfers the numerals without the clinical meaning. The practical effect would be to strip coverage from the third of beneficiaries with the best expected transplant outcomes and the lowest treatment-related mortality.

Third, the language as written is unadministrable. A patient can be ISS stage I but R-ISS stage II, or ISS stage I but R2-ISS stage III, on the basis of del(17p), t(4;14), or 1q abnormalities. The phrase “ISS and its revisions” does not specify which system governs when they disagree. R2-ISS also has four stages, so a plain reading of “stage II or III” would exclude R2-ISS stage IV, the highest-risk group in that system. Hundreds of transplant programs and Medicare contractors would each resolve these ambiguities differently.

Fourth, no clinical guideline and no other major payer uses stage as a gatekeeper for transplantation. NCCN, ASTCT, IMWG, and the EHA-ESMO guidelines cited in the memorandum all recommend transplant for transplant-eligible newly diagnosed myeloma regardless of stage. Eligibility rests on the presence of active disease requiring therapy under IMWG criteria, together with adequate organ function and fitness, which the NCD already requires.

Requested change: strike the staging requirement from section B.II.b, so that single AuSCT is covered for beneficiaries with newly diagnosed or responsive multiple myeloma and adequate cardiac, renal, pulmonary, and hepatic function. If CMS concludes that a staging reference must remain, the language should read “ISS stages I, II, or III, or the corresponding stages of its revisions.”
Thank you for the opportunity to comment.

Sincerely,

Faiz Anwer, M.D., F.A.C.P.
Professor of Medicine, Department of Medicine
Cleveland Clinic Lerner College of Medicine
Case Western Reserve University School of Medicine
Multiple Myeloma Program
Hematology, Oncology, Stem Cell Transplantation
Director, Inpatient Lymphoma Myeloma Service
Taussig Cancer Center, 9500 Euclid Ave, CA60, Cleveland, OH 44195
Cleveland Clinic, 10201 Carnegie Ave, Cleveland, OH 44195
Fax: 216-444-9464

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Thank you for reviewing the NCD around autologous stem cell transplantation (ASCT) coverage in multiple myeloma. In brief, many of us realized too late that the letter you received dated June 9, 2025 (signed by Oliver Kim, whom I have spoken directly with) incorrectly stated the question at hand. The question is not whether Durie-Salmon or ISS staging is superior; instead, it is whether staging has any relevance toward ASCT eligibility or outcomes in multiple myeloma. The short answer is no. There is no reason why Stage 1 patients should be deprived of access to ASCT. All clinical trials in the modern era of newly diagnosed myeloma have included Stage 1 patients regardless of what staging criteria are used. Similarly, neither commercial insurers nor any transplant physician in the country use staging of any type to determine who will benefit from transplantation versus who won't.

I have spoken with leadership at ASH and IMF (who had signed onto the original letter), and they were not aware of this letter - nor were any of us in the myeloma field. We ask that staging should be removed entirely from ASCT eligibility criteria for myeloma to avoid disparities for Medicare patients. They should have the same access to care as Americans with commercial insurance. Alternatively, if it more appropriate to list that ISS Stage 1-3 patients are eligible (namely, including Stage 1), that is sufficient as well.

We are working as a field urgently to generate more public comments, including from professional societies, to supplement these individual comments. Thank you again for your consideration, and - as a myeloma expert myself - I am sincerely apologetic that our field did not provide you with the correct request back in 2025. We are working to fix this now!

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I support the request per the explanation in the letter because there is additional scientific evidence regarding the use of ISS and its revisions when identifying covered indications of multiple myeloma. This evidence was not considered during the most recent review of NCD §110.23, and if it had been considered, it would have warranted a change to the NCD decision for AuSCT. The adoption of ISS as a preferred staging system for multiple myeloma is well supported in the medical literature, which we include as a list of citations in the appendix. Durie-Salmon was developed in 1975 and utilized clinical parameters that were “commonly available” at that time, but clinical advances have led to more contemporary prognostic staging systems.3 For example, the National Comprehensive Cancer Network (NCCN) references ISS and the two ISS revisions in its version 4.2024 guidelines.'

American Society of Hematology
Association of Cancer Care Centers
Corewell Health
International Myeloma Foundation
Medical University of South Carolina, Hollings Cancer Center

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